Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.7 (plasmin)
9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating blood plasma contains proteinase-degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzyme-linked immunosorbent assay using a monoclonal antibody to protease-degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 +/- 6.2 ng/ml: means +/- SD) compared with the levels in normal controls (8.0 +/- 1.9 ng/ml, n = 20) (P less than 0.001). Fibrin degradation products (D-dimer), thrombin-antithrombin III complex, and plasmin alpha 2-antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin-mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P less than 0.0001). The plasma levels of thrombomodulin and E-alpha 1PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti-leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E-alpha 1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P less than 0.001). These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease-degraded fragments of it into the circulation.
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PMID:Increased levels of plasma thrombomodulin in chronic myelogenous leukemia. 131 1

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.
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PMID:[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism]. 131 73

Heparin is indispensable anticoagulant for cardiopulmonary bypass, but the dose of heparin is even now under discussion. In this study, hemostatic fluctuation was analyzed during and after the bypass using hemostatic molecular markers. The subjects were 16 adult cases of open heart surgery, 12 males, 4 females. The average age was 55.0 year. Operations were aortocoronary bypass in 12, valvular surgery in 3 and ASD patch closure in one with moderate hypothermic cardiopulmonary bypass. At the beginning of cardiopulmonary bypass, 3 mg/kg heparin was administered and the equivalent amount of protamine sulfate was used for neutralization at the end of the bypass. Platelet count, hematocrit, antithrombin III (ATIII), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, thrombin antithrombin III complex, FDP, D dimer FDP, plasmin alpha 2 plasmin inhibitor complex, tissue plasminogen activator (t-PA), and thrombomodulin (TM) were measured through the operation up to two weeks after surgery. ATIII decreased to 50% of control value all through the bypass. Platelet markers increased immediately, and the activated state continued 3 hours after the bypass. Coagulation markers increased markedly after the aortic declamping, and reached at its peak by three times as control value, immediately after the protamine neutralization and continued for 3 hours. During the bypass, fibrinogenolysis caused by t-PA which was stimulated by non-physiological circulation and stimulating substances, was observed. Fibrinolysis occurred following the hypercoagulability after the neutralization. TM was within normal range before the aortic declamping. But increased gradually after the declamp, and reached twice as much as the base line. It could be concluded that hypercoagulability and high platelet activation might play a role of perioperative thrombosis. Hypercoagulability and increase of serum TM would be related to reperfusion of the lung. The increasing of TM would reflect broad injury of vessel walls after the bypass, because plasma TM increased following the generalized injury of endothelial cells.
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PMID:[A clinical study on hemostatic fluctuation during and after cardiopulmonary bypass using hemostatic molecular markers]. 133 89

Plasma levels of thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex were measured by ELISA in patients with rheumatic diseases. Thrombomodulin levels in patients with active systemic lupus erythematosus (SLE) were significantly higher than those in patients with inactive SLE or in healthy controls. This suggests that thrombomodulin, normally a component of vascular endothelial cell membrane, is easily released to plasma in patients with active SLE. High titers of the thrombomodulin level and the correlated alpha 2-plasmin inhibitor-plasmin complex elevations imply vascular injury, and consequently, excessive fibrinolytic processes in active SLE.
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PMID:Plasma thrombomodulin and alpha 2-plasmin inhibitor-plasmin complex are elevated in active systemic lupus erythematosus. 133 9

Plasma levels of molecular markers of hemostatic activation were investigated in 205 samples from patients with haematopoietic malignancies. These markers included thrombin/antithrombin III complex (TAT), D-dimer, plasmin/alpha 2plasmin inhibitor complex (PIC) and thrombomodulin (TM), and were assayed by EIA methods. Samples were divided into 4 groups according to the level of FDP: group A; FDP 10 greater than, group B; 10 less than or equal to less than 20 group C; 20 less than or equal to less than 40, and group D; less than 40. The mean level of each marker except TM increased in the order of group A, B, C and D. However, in many samples belonging to group A the plasma TAT or PIC levels and both were increased in spite of low FDP level. Furthermore, levels of TAT and PIC in several samples belonging to groups C and D were within the normal range. Also, the mean levels of each marker except TM increased in the order of 2, 3, 4, 5 and over 6 points in DIC score according to the criteria of DIC diagnosis by the research committee on DIC of the Ministry of Health and Welfare in Japan. Eight of the 11 samples (72.7%) obtained from cases with a DIC score of 3 points had high plasma levels of TAT, PIC and D-dimer. Plasma levels of these markers were increased after chemotherapy. These findings lead to the following conclusions: 1) FDP reflexed activation of coagulation and fibrinolysis, but 2) FDP was not more sensitive than TAT and PIC, and 3) the increase of FDP rarely resulted from fibrinogenolysis or non-plasmin mediated fibrinolysis. Furthermore, 4) TAT, D-dimer and PIC may serve as sensitive parameters of hemostatic activation in circulating blood and be valuable markers for early diagnosis of DIC.
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PMID:[Clinical application of laboratory diagnosis: leukemia and DIC]. 183 71

Binding of 125I-thrombin to endothelial cells derived from human umbilical vein was studied in tissue culture. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography revealed covalent binding of thrombin in a 72-kDa complex. This binding is specific and requires the catalytically active site of the enzyme. Formation of the complex could be detected as early as 3 min after addition of thrombin or with a thrombin concentration as low as 0.5 nM. This irreversible binding exhibits thrombin dose-dependence and reaches maximum levels at a concentration of 50 nM (10 fmol/10(5) cells). Some characteristics of the 72-kDa complex were compared to those of the complexes formed between thrombin and protease nexin originating from fibroblasts or platelets: (i) its electrophoretic mobility on SDS-PAGE is identical to that of the thrombin-platelet protease nexin complex, (ii) heparin prevents the appearance of the complex on the cell surface, (iii) plasmin in a 100-fold molar excess prevents the covalent linkage of thrombin, suggesting that the protease specificity of the endothelial component involved in the complex might not be restricted to thrombin. Yet no release, nor any secretion of the endothelial protein, could be detected. These results indicate that active thrombin binds covalently to a specific endothelial protein that is in several respects similar to fibroblast or platelet protease nexin and provides a thrombin binding site distinct from thrombomodulin and glycosaminoglycans.
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PMID:Covalent binding of human thrombin to a human endothelial cell-associated protein. 252 28

The important role of protein C (PC) in the regulation of hemostasis has been appreciated since the description of patients who were deficient in PC and presented with severe thromboembolic events. The potentially fatal complications associated with PC-deficiency require an early and reliable identification of those patients affected with this inherited disorder. The present study introduces a test procedure for the functional assessment of PC in plasma samples. The test utilizes the thrombin/thrombomodulin complex to achieve complete and rapid formation of activated PC whose proteolytic capacity is subsequently determined with a chromogenic substrate. Homogenate obtained from rabbit lung effectively substituted the purified component thrombomodulin in the assay system. This new approach simplifies the test procedure without losing specificity and accuracy. Proteases, such as plasmin, streptokinase and urokinase did not influence the assay and the inhibitory effect of heparin on the PC-activation could easily be overcome by the addition of protamine sulphate. The PC-activity in a group of unselected patients (n = 50), who did not reveal any abnormalities in global coagulation tests, amounted to 100 +/- 12% (mean +/- SD) with a range from 54 to 143% when analyzed in comparison to a plasma pool constituted from healthy volunteers. Since the synthesis of PC depends on the availability of vitamin K, patients receiving phenprocoumon have also been analyzed. These patients (n = 103) presented 40 +/- 11% residual PC-activity accompanied by a concomitant decrease in PC-antigen levels to 43 +/- 10% (mean +/- SD). The test described is specific, sensitive, less time-consuming and can be performed on a routine basis.
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PMID:A simplified functional assay for protein C in plasma samples. 351 73

Numerous investigators have postulated that a hypercoagulable state exists in humans for a period of time before the development of thrombotic episodes. A clear biochemical definition of the prethrombotic state, however, has proved elusive due in part to the lack of reliable techniques for monitoring pertinent changes in blood coagulability. Based on recent advances in our knowledge of the biochemistry of the coagulation system, a series of highly sensitive and specific immunochemical tools has been developed that can quantitate the activities of various steps of the hemostatic mechanism in vivo at the subnanomolar level. We have established assays for F1+2 and the protein C activation peptide, which measure the cleavage of the prothrombin molecule by factor Xa and the scission of protein C by the thrombin-thrombomodulin complex, respectively. Nossel and coworkers had previously constructed similar assays for fibrinopeptide A (FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by thrombin and the proteolysis of fibrin I by plasmin, respectively. Substantial elevations in the levels of these markers have been found in patients with disseminated intravascular coagulation and many subjects with acute deep venous thrombosis. The F1+2 and FPA assays have been used to demonstrate that significant increments in factor Xa activity but not thrombin activity regularly occur in the blood of nonanticoagulated individuals with congenital deficiencies of antithrombin or protein C. These two disorders are known to be correlated with the subsequent development of thrombosis. Patients with protein C deficiency have also been noted to have significantly reduced plasma levels of protein C activation peptide. By using the immunoassays for FPA and B beta 1-42 in studies of postoperative patients, it has been shown that an imbalance between the procoagulant action of thrombin and the anticoagulant effect of plasmin on fibrin I polymer may induce an acquired thrombotic diathesis. Finally, we have recently demonstrated that prothrombin activation as measured by the F1+2 assay is suppressed by oral anticoagulants in the blood of patients with thrombotic diatheses. These investigations suggest that these assay techniques can be used to improve our understanding of the hypercoagulable state as well as to develop more effective treatment strategies for the prevention of thromboembolic events.
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PMID:The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. 360 75

We investigated the effect of plasmin on the integrity and function of endothelial cells to elucidate the mechanism by which bleeding or rethrombosis may be induced in thrombolytic therapy. When incubated with cultured human umbilical vein endothelial cells (HUVECs), plasmin increased the endothelial permeability to serum albumin 10 minutes after the incubation. Plasmin damaged the cell membranes 30 minutes after the incubation, detached the cells from the matrix 3 hours after the incubation, and finally induced cell lysis. Such damaging effects on HUVECs were not observed with plasminogen or plasmin pretreated with aprotinin and alpha 2-plasmin inhibitor, suggesting that the catalytic function of plasmin plays an important role in inducing this damage. Sulfur 35-labeled glycosaminoglycans (35S-GAGs) of HUVECs were decreased 1 hour after the incubation of plasmin with HUVECs, and the thrombomodulin (TM) activity of HUVECs measured by protein C activation capacity was decreased 6 hours after the incubation. Neither 35S-GAGs nor the TM activity of HUVECs was decreased after the incubation of plasmin pretreated with aprotinin and alpha 2-plasmin inhibitor. These findings suggest that the nonthrombogenic properties of endothelial cells can be damaged by the proteolytic action of plasmin. Our findings, taken together, suggest that plasmin damages the endothelial barrier function, endothelial cell integrity, and nonthrombogenic properties. These damaging effects of plasmin on endothelial cells may be related to the pathophysiology of bleeding or rethrombosis observed in patients undergoing high-dose thrombolytic therapy for thrombosis.
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PMID:Endothelial cell injury induced by plasmin in vitro. 756 47

To investigate the relationship between changes in plasma concentrations of polymorphonuclear elastase (PMN-E) and haemostatic effects during haemodialysis (HD), changes in the plasma concentrations of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and fibrinogen (Fbg), cross-linked fibrin degradation products (XDP), thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC) and soluble thrombomodulin (TM) in 49 patients with end-stage chronic glomerulonephritis maintained on chronic HD were measured. Plasma concentrations of TAT, PIC, TM and E-alpha 1 PI significantly increased during a single HD. There was a statistically significant correlation between change in plasma E-alpha 1 PI concentration and changes in plasma concentrations of TAT, PIC and TM during a single HD, as well as between changes in plasma concentrations of TM and TAT during a single HD. These observations suggested that activation of coagulation and fibrinolysis, endothelial cell damage, and activation of polymorphonuclear cells occur during HD. Activation of polymorphonuclear cells may induce activation of coagulation and fibrinolysis, leading to endothelial cell damage, augmented by release of proteases such as elastase.
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PMID:Relationship between elevation in the plasma concentration of elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and haemostatic parameters during haemodialysis. 779 53


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